Monkey business Monkeys, like humans, become more forgetful as they grow older. Now, a new study has captured the decline in the performance of brain memory circuits as monkeys age.

The study, reported in this week's Nature, sheds light on the normal processes of ageing in monkeys, and offers hope for improvement.

Professor Amy Arnsten and colleagues at Yale University looked at the brain region associated with spatial working memory in six Rhesus macaque monkeys.

Like other types of working memory, spatial working memory holds information for only a short time, but it is the key to effective everyday functioning.

"It's the memory you use when you ask yourself, 'Now where did I leave my car keys this time?'," says Arnsten.

She says because spatial working memory is constantly having to update it is important it does not become confused by similar previous information - like where you put your keys yesterday.

For the latest study, the monkeys had to remember where a flashing light had most recently appeared on a computer screen.

The light could appear in one of eight different positions, assigned randomly. If, after a brief delay, the monkeys remembered the most recent position of the flashing light correctly, they earned a reward of their favourite juice.

During this trial electrical recordings were being made from about 50 neurons in the prefrontal cortex (the brain region holding spatial working memory) of each monkey.

Two of the monkeys were young (seven and nine years), two were middle-aged (12 and 13 years) and two were old (17 and 21 years).

The study found there were age-dependent differences in the response of a particular group of neurons in the monkeys - called 'delay' neurons.

"These neurons have been known about for two decades," says Arnsten.

Weaker recall

The neurons literally hold the memory 'in mind' by continuing to fire even though there is no outside stimulation. They form an excitatory network, keeping each other firing through connections known as dendritic spines, she says. If the delay neurons stop firing, the memory is lost.

While doing the task, the middle-aged and the elderly monkeys showed much lower firing rates in their delay neurons, than the young monkeys. Although the older monkeys did manage to remember correctly most of the time, their memories were clearly held much more weakly.

Arnsten says this fits with what we see in middle-aged and elderly people. "It is harder to shift attention and harder to hold things in mind especially in the presence of distractions."

So what is causing the decline in firing of the delay cells? Arnsten and her team suggest increased levels of a key messenger molecule called cylic AMP (cAMP) are causing potassium channels on the delay neurons to open, which makes firing of the neurons less likely.

They found by applying minute quantities of drugs that either reduce cAMP levels or block the potassium channels, the delay neurons in the older monkeys would fire at rates similar to those seen in the young animals.

One of these drugs (guanfacine) is used to treat high blood pressure. A separate group of researchers at Yale University are already conducting clinical trials to see whether guanfacine is helpful in improving working memory in people aged over 75 years.

Associate Professor Sharon Naismith of the Brain and Mind Research Institute at the University of Sydney looks for interventions that can improve cognitive function in the elderly.

She says the study is valuable because it identifies changes in the delay neurons.

"It's also nice that they've applied an intervention," she says.

"As people age they just can't hold as much in their working memory, and taking in conversations and things they see on the news becomes difficult. You even need working memory for things like cooking."

This paper tackles the basic science, says Naismith. "Of course, we have to understand normal ageing first before we can really target diseases like Alzheimer's," she says.